Recently, the 123I-amines, N-isopropyl-P-123 I-iodoamphetamine (123I-IMP) and N,N,N'-Trimethyl-N'-(2-hydroxy-3-methyl-5-123I-iodobenzyl)-1,3-prpanediamine (123I-HIPDM) have been proposed as agents for the measurement of cerebral blood flow in pathology. In this proposal we wish to study the relationship between the distribution of these 123I-amines in various conditions to ascertain whether they can be used as quantitative indicators of cerebral blood flow and to study the mechanism of brain uptake and retention. These new agents have potential use both in the study of many pathological conditions, both in animal models using autoradiography and in humans using single photon emission tomography (SPECT). To use these indicators with autoradiography in animals and with SPECT in humans, we propose to extend the measurement interval from 30 sec or 5 min. We also propose to compare these two 123I-amines in pathological conditions to evaluate their usefulness as CBF agents in human pathology. The brain extraction and blood flow will be determined under conditions of varying arterial pH and amine specific activity to evaluate the mechanism of bran uptake and retention. The techniques needed for this study have been developed in this laboratory and involve the use of 123I and 14C labeled tracers using quantitative double radionuclide autoradiography. The direct evaluation of the 123I-amines distribution will be compared to CB1, as measured with the established CBF tracer, 14C-iodoantipyrine on a highly regional basis. The mechanism of 123I-amines brain uptake and retention is not known exactly, but has been proposed to be due to either their high lipid solubility, their interaction with nonspecific amine binding situes, or some influence exerted by the pH gradient across the brain blood barrier. The study of the behavior of these 123I-amines during stroke, epilepsy, in the ibotenic acid lesion model, and as a function of pH and amine specific activity will define the brain uptake mechanism and usefulness of the I-123 amines as CBF tracers.